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Project Bibliography

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Mesnage et al., 2019

Mesnage, R., Benbrook, C., & Antoniou, M. N.; “Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides;” Food and Chemical Toxicology, 2019, 128, 137-145; DOI: 10.1016/j.fct.2019.03.053.

ABSTRACT:

Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are approximately 100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required. FULL TEXT


Pahwa et al., 2019

Pahwa, M., Beane Freeman, L. E., Spinelli, J. J., Blair, A., McLaughlin, J. R., Zahm, S. H., Cantor, K. P., Weisenburger, D. D., Punam Pahwa, P. P., Dosman, J. A., Demers, P. A., & Harris, S. A.; “Glyphosate use and associations with non-Hodgkin lymphoma major histological sub-types: findings from the North American Pooled Project;” Scandinavian Journal of Work, Environment, & Health, 2019; DOI: 10.5271/sjweh.3830.

ABSTRACT:

OBJECTIVES:

Some epidemiological studies have suggested positive associations between glyphosate use and non-Hodgkin lymphoma (NHL), but evidence is inconsistent and few studies could evaluate histological sub-types. Here, associations between glyphosate use and NHL incidence overall and by histological sub-type were evaluated in a pooled analysis of case-control studies.

METHODS:

The analysis included 1690 NHL cases [647 diffuse large B-cell lymphoma (DLBCL), 468 follicular lymphoma (FL), 171 small lymphocytic lymphoma (SLL), and 404 other sub-types] and 5131 controls. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for NHL overall and sub-types with self-reported ever/never, duration, frequency, and lifetime-days of glyphosate use.

RESULTS:

Subjects who ever used glyphosate had an excess of NHL overall (OR 1.43, 95% CI 1.11-1.83). After adjustment for other pesticides, the OR for NHL overall with “ever use” was 1.13 (95% CI 0.84-1.51), with a statistically significant association for handling glyphosate >2 days/year (OR 1.73, 95% CI 1.02-2.94, P-trend=0.2). In pesticide-adjusted sub-type analyses, the ordinal measure of lifetime-days was statistically significant (P=0.03) for SLL, and associations were elevated, but not statistically significant, for ever years or days/year of use. Handling glyphosate >2 days/year had an excess of DLBCL (OR 2.14, 95% CI 1.07-4.28; P-trend=0.2). However, as with the other sub-types, consistent patterns of association across different metrics were not observed.

CONCLUSIONS:

There was some limited evidence of an association between glyphosate use and NHL in this pooled analysis. Suggestive associations, especially for SLL, deserve additional attention. FULL TEXT


Sagiv et al., 2019

Sagiv, S. K., Bruno, J. L., Baker, J. M., Palzes, V., Kogut, K., Rauch, S., Gunier, R., Mora, A. M., Reiss, A. L., & Eskenazi, B.; “Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application;” Proceedings of the National Academy of Sciences of the United States of America, 2019; DOI: 10.1073/pnas.1903940116.

ABSTRACT:

We have reported consistent associations of prenatal organophosphate pesticide (OP) exposure with poorer cognitive function and behavior problems in our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort of Mexican American youth in California’s agricultural Salinas Valley. However, there is little evidence on how OPs affect neural dynamics underlying associations. We used functional near-infrared spectroscopy (fNIRS) to measure cortical activation during tasks of executive function, attention, social cognition, and language comprehension in 95 adolescent CHAMACOS participants. We estimated associations of residential proximity to OP use during pregnancy with cortical activation in frontal, temporal, and parietal regions using multiple regression models, adjusting for sociodemographic characteristics. OP exposure was associated with altered brain activation during tasks of executive function. For example, with a 10-fold increase in total OP pesticide use within 1 km of maternal residence during pregnancy, there was a bilateral decrease in brain activation in the prefrontal cortex during a cognitive flexibility task (β = -4.74; 95% CI: -8.18, -1.31 and β = -4.40; 95% CI: -7.96, -0.84 for the left and right hemispheres, respectively). We also found that prenatal OP exposure was associated with sex differences in brain activation during a language comprehension task. This first functional neuroimaging study of prenatal OP exposure suggests that pesticides may impact cortical brain activation, which could underlie previously reported OP-related associations with cognitive and behavioral function. Use of fNIRS in environmental epidemiology offers a practical alternative to neuroimaging technologies and enhances our efforts to assess the impact of chemical exposures on neurodevelopment. FULL TEXT


Gage et al., 2019

Gage, Karla L., Krausz, Ronald F., & Walters, S. Alan; “Emerging Challenges for Weed Management in Herbicide-Resistant Crops;” Agriculture, 2019, 9(8); DOI: 10.3390/agriculture9080180.

ABSTRACT:

Since weed management is such a critical component of agronomic crop production systems, herbicides are widely used to provide weed control to ensure that yields are maximized. In the last few years, herbicide-resistant (HR) crops, particularly those that are glyphosate-resistant, and more recently, those with dicamba (3,6-dichloro-2-methoxybenzoic acid) and 2,4-D (2,4-dichlorophenoxyacetic acid) resistance are changing the way many growers manage weeds. However, past reliance on glyphosate and mistakes made in stewardship of the glyphosate-resistant cropping systemhave directly led to the current weed resistance problems that now occur in many agronomic cropping systems, and new technologies must be well-stewarded. New herbicide-resistant trait technologies in soybean, such as dicamba-, 2,4-D-, and isoxaflutole- ((5-cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone) resistance, are being combined with glyphosate- and glufosinate-resistance traits to manage herbicide-resistant weed populations. In cropping systems with glyphosate-resistant weed species, these new trait options may provide effective weed management tools, although there may be increased risk of off-target movement and susceptible plant damage with the use of some of these technologies. The use of diverse weed management practices to reduce the selection pressure for herbicide-resistant weed evolution is essential to preserve the utility of new traits. The use of herbicides with differing sites of action (SOAs), ideally in combination as mixtures, but also in rotation as part of a weed management program may slow the evolution of resistance in some cases. Increased selection pressure from the effects of some herbicide mixtures may lead to more cases of metabolic herbicide resistance. The most effective long-term approach for weed resistance management is the use of Integrated Weed Management (IWM) which may build the ecological complexity of the cropping system. Given the challenges in management of herbicide-resistant weeds, IWM will likely play a critical role in enhancing future food security for a growing global population. FULL TEXT


Curl et al., 2019

Curl, C. L., Porter, J., Penwell, I., Phinney, R., Ospina, M., & Calafat, A. M.; “Effect of a 24-week randomized trial of an organic produce intervention on pyrethroid and organophosphate pesticide exposure among pregnant women;” Environment International, 2019, 104957; DOI: 10.1016/j.envint.2019.104957.

ABSTRACT:

BACKGROUND: Introduction of an organic diet can significantly reduce exposure to some classes of pesticides in children and adults, but no long-term trials have been conducted.

OBJECTIVES: To assess the effect of a long-term (24-week) organic produce intervention on pesticide exposure among pregnant women.

METHODS: We recruited 20 women from the Idaho Women, Infants, and Children (WIC) program during their first trimester of pregnancy. Eligible women were nonsmokers aged 18-35 years who reported eating exclusively conventionally grown food. We randomly assigned participants to receive weekly deliveries of either organic or conventional fruits and vegetables throughout their second or third trimesters and collected weekly spot urine samples. Urine samples, which were pooled to represent monthly exposures, were analyzed for biomarkers of organophosphate (OP) and pyrethroid insecticides.

RESULTS: Food diary data demonstrated that 66% of all servings of fruits and vegetables consumed by participants in the “organic produce” group were organic, compared to <3% in the “conventional produce” group. We collected an average of 23 spot samples per participant (461 samples total), which were combined to yield 116 monthly composites. 3-Phenoxybenzoic acid (3-PBA, a non-specific biomarker of several pyrethroids) was detected in 75% of the composite samples, and 3-PBA concentrations were significantly higher in samples collected from women in the conventional produce group compared to the organic produce group (0.95 vs 0.27mug/L, p=0.03). Another pyrethroid biomarker, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, was detected more frequently in women in the conventional compared to the organic produce groups (16% vs 4%, p=0.05). In contrast, we observed no statistically significant differences in detection frequency or concentrations for any of the four biomarkers of OP exposure quantified in this trial.

DISCUSSION: To our knowledge, this is the first long-term organic diet intervention study, and the first to include pregnant women. These results suggest that addition of organic produce to an individual’s diet, as compared to conventional produce, significantly reduces exposure to pyrethroid insecticides. FULL TEXT


Jusko et al., 2012

Jusko, T. A., Klebanoff, M. A., Brock, J. W., & Longnecker, M. P.; “In-utero exposure to dichlorodiphenyltrichloroethane and cognitive development among infants and school-aged children;” Epidemiology, 2012, 23(5), 689-698; DOI: 10.1097/EDE.0b013e31825fb61d.

ABSTRACT:

BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) continues to be used for control of infectious diseases in several countries. In-utero exposure to DDT and dichlorodiphenyldichloroethylene (DDE) has been associated with developmental and cognitive impairment among children. We examined this association in an historical cohort in which the level of exposure was greater than in previous studies.

METHODS: The association of in-utero DDT and DDE exposure with infant and child neurodevelopment was examined in 1100 subjects in the Collaborative Perinatal Project, a prospective birth cohort enrolling pregnant women from 12 study centers in the United States from 1959 to 1965. Maternal DDT and DDE concentrations were measured in archived serum specimens. Infant mental and motor development was assessed at age 8 months using the Bayley Scales of Infant Development, and child cognitive development was assessed at age 7 years, using the Wechsler Intelligence Scale for Children.

RESULTS: Although levels of DDT and DDE were relatively high in this population (median DDT concentration, 8.9 mug/L; DDE, 24.5 mug/L), neither were related to Mental or Psychomotor Development scores on the Bayley Scales nor to Full-Scale Intelligence Quotient at 7 years of age. Categorical analyses showed no evidence of dose- response for either maternal DDT or DDE, and estimates of the association between continuous measures of exposure and neurodevelopment were indistinguishable from 0.

CONCLUSIONS: Adverse associations were not observed between maternal serum DDT and DDE concentrations and offspring neurodevelopment at 8 months or 7 years in this cohort. FULL TEXT


Duty et al., 2003

Duty, S. M., Singh, N. P., Silva, M. J., Barr, D. B., Brock, J. W., Ryan, L., Herrick, R. F., Christiani, D. C., & Hauser, R.; “The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay;” Environmental Health Perspectives, 2003, 111(9), 1164-1169; DOI: 10.1289/ehp.5756.

ABSTRACT:

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.  FULL TEXT


Wenzel et al., 2018

Wenzel, A. G., Brock, J. W., Cruze, L., Newman, R. B., Unal, E. R., Wolf, B. J., Somerville, S. E., & Kucklick, J. R.; “Prevalence and predictors of phthalate exposure in pregnant women in Charleston, SC;” Chemosphere, 2018, 193, 394-402; DOI: 10.1016/j.chemosphere.2017.11.019. https://www.ncbi.nlm.nih.gov/pubmed/29154114.

ABSTRACT:

Phthalates are plasticizers commonly detected in human urine due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogenic endocrine disruptors, which raises concern for prenatal exposure during critical windows of fetal development. While phthalate exposure is ubiquitous, certain demographics are subject to greater or lesser exposure. We sampled urine from 378 pregnant women during the second trimester of gestation living in Charleston, SC, and measured eight urinary phthalate metabolites as biomarkers of phthalate exposure: monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and monomethyl phthalate (MMP). Demographic data was collected from questionnaires administered at the time of specimen collection. All phthalate metabolites were detected in over 93% of urine samples. On average, concentrations were highest for MEP (median = 47.0 ng/mL) and lowest for MMP (median = 1.92 ng/mL). Sociodemographic characteristics associated with elevated phthalate concentrations included being unmarried, less educated, having a low income, high body mass index (BMI), and/or being African American. After racial stratification, age, BMI, education, and income were significantly associated with phthalate concentrations in African American women. Marital status was associated with phthalate concentrations in Caucasian women only, with greater concentrations of MBP, MEHHP, MiBP, and MMP in unmarried versus married women. Results of this cross-sectional study provide evidence for significant racial and demographic variations in phthalate exposure. FULL TEXT


Silva et al., 2003

Silva, M. J., Malek, N. A., Hodge, C. C., Reidy, J. A., Kato, K., Barr, D. B., Needham, L. L., & Brock, J. W.; “Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry;” Journal of Chromatography Part B: Analytical Technologies in the Biomedical and Life Sciences, 2003, 789(2), 393-404.

ABSTRACT:

Phthalates are widely used as industrial solvents and plasticizers, with global use exceeding four million tons per year. We improved our previously developed high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric (HPLC-APCI-MS/MS) method to measure urinary phthalate metabolites by increasing the selectivity and the sensitivity by better resolving them from the solvent front, adding three more phthalate metabolites, monomethyl phthalate (mMP), mono-(2-ethyl-5-oxohexyl)phthalate (mEOHP) and mono-(2-ethyl-5-hydroxyhexyl)phthalate (mEHHP); increasing the sample throughput; and reducing the solvent usage. Furthermore, this improved method enabled us to analyze free un-conjugated mono-2-ethylhexyl phthalate (mEHP) by eliminating interferences derived from coelution of the glucuronide-bound, or conjugated form, of the mEHP on measurements of the free mEHP. This method for measuring phthalate metabolites in urine involves solid-phase extraction followed by reversed-phase HPLC-APCI-MS/MS using isotope dilution with (13)C(4) internal standards. We further evaluated the ruggedness and the reliability of the method by comparing measurements made by multiple analysts at different extraction settings on multiple instruments. We observed mMP, monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mEHP, mEHHP and mEOHP in the majority of urine specimens analyzed with DEHP-metabolites mEHHP and mEOHP present in significantly higher amounts than mEHP.


Kleter et al., 2011

Kleter, Gijs A, Unsworth, B, & Harris, Caroline A; “The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues;” Pest Management Science, 2011, 67, 1193-1210; DOI: 10.1002/ps.2128.

ABSTRACT:

The global area covered with transgenic (genetically modified) crops has rapidly increased since their introduction in the mid-1990s.Most of these crops have been rendered herbicide resistant, for which it can be envisaged that the modification has an impact on the profile and level of herbicide residues within these crops. In this article, the four main categories of herbicide resistance, including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate and glyphosate, are reviewed. The topics considered are the molecular mechanism underlying the herbicide resistance, the nature and levels of the residues formed and their impact on the residue definition and maximum residue limits (MRLs) defined by the Codex Alimentarius Commission and national authorities. No general conclusions can be drawn concerning the nature and level of residues, which has to be done on a case-by-case basis. International residue definitions and MRLs are still lacking for some herbicide–crop combinations, and harmonisation is therefore recommended. FULL TEXT


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